What is the main side effect of the antimetabolite methotrexate?

The main side effect of the antimetabolite methotrexate is bone marrow suppression. This occurs because methotrexate inhibits the metabolism of folic acid, which is essential for the synthesis of nucleotides needed for DNA and RNA production. The bone marrow is particularly sensitive to this effect because it rapidly produces blood cells, including red blood cells, white blood cells, and platelets.

As a result, patients treated with methotrexate may experience myelosuppression, which can lead to anemia, increased risk of infections due to lower white blood cell counts, and a greater likelihood of bleeding due to decreased platelet production. This side effect is significant and requires monitoring of blood counts during treatment to manage and mitigate risks associated with such therapy.

Consideration of other options reveals that hypotension, weight loss, and hypoglycemia are not the primary or common side effects associated with methotrexate, making them less relevant in the context of its major adverse effects.